The initial publication of cross-sectional results from DIAN validate the use of AD biomarkers to identify preclinical AD, as only MCs (both asymptomatic and symptomatic) demonstrated biomarker abnormalities. Although preliminary, the findings propose an instructive timeline for the pathophysiology of preclinical AD, beginning with elevated CSF Aβ42 that presumably is present at birth but at perhaps 20-25 years prior to estimated AAO of symptomatic AD begins to decline. The DIAN study will provide the infrastructure for randomized, placebo-controlled secondary prevention trials of mechanism-based therapies in ADAD. The trials will be designed to allow several therapies to be evaluated simultaneously, with an initial primary outcome of target engagement and multiple secondary outcomes of downstream AD biomarkers. The compound(s) with the optimal target engagement, improvement of neurodegenerative biomarkers, and sufficient safety profile then will be selected for a second trial in which cognitive benefit will be the primary outcome. In this session, discuss the early results of the DIAN trial as well as review key highlights and information.

•Analyze the importance of the DIAN trial to Alzheimer’s clinical trials

•Discuss the therapies being evaluated in the DIAN trial and study design